GENOSEPT Berichtzusammenfassung

Final Report Summary - GENOSEPT (Genetics of sepsis in Europe)

The ultimate aim of the GENOSEPT project was to link European intensive care clinicians with laboratory scientists to enhance public understanding of how genetics affects the patients' outcome from severe sepsis or septic shock. The project assumed that susceptibility to expensive new treatments and fatal outcomes from severe sepsis were partially genetically determined. The project tested this hypothesis using gene expression studies to define novel candidate genes including those controlling programmed cell death. The novel candidate genes identified would then be analysed in subsequent epidemiologic studies of genetic predisposition to sepsis-related mortality and morbidity in European intensive care units. The European Society of Intensive Care Medicine (ESICM) would coordinate a consortium of leading experts in sepsis, genomics, genetic epidemiology, biometrics and genetic high-throughput genotyping to link this new science to patient-centred outcomes.

The project sought to provide important data on gender-related mortality and morbidity. It would have a major impact on diagnosis and treatment of European sepsis patients in subsequent therapeutic trials by targeting risk sub-populations and focusing expensive new treatments. Furthermore, it would also standardise protocols for genotyping, facilitate application of new knowledge in functional and structural genomics, harmonise high-throughput genotyping and quality control between major European centres, as well as contribute to reducing sepsis-related mortality in European healthcare.

Amongst the results achieved were the following: - the development of electronic Case report forms (eCRFs); - the engagement of national coordinators in their role in helping their local Intensive care units (ICUs) recruit patients for the study; - obtained ethics approval for ICUs in Europe and Israel; - the recruitment of more than 2500 patient Europe-wide (and Israel) for genome wide genotyping; - the verification of the quality and content of the eCRFs for each patient; - the process of blood samples for genotyping; - the evaluation of candidate genes and markers suitable for genotyping relative to sepsis; - the evaluation of genotyping tests; - the evaluation of study designs for the genotyping; - the pursue of a scientific and statistical analysis of the first step of genotyping and association of the genetic variants with the primary study endpoint, namely the mortality; - the pursue of a statistical analysis of genotype versus phenotype of patients; - the promotion of genomic research in eastern European countries.